title: Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies.
abstract: An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.
authors.affiliation: Department of Pediatrics, UCSF Medical Center, University of California, San Francisco, CA 94143-1278, USA. hornb@peds.ucsf.edu
authors.forename: B
authors.initials: B
authors.lastname: Horn
authors.forename: S
authors.initials: S
authors.lastname: Soni
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: A
authors.initials: A
authors.lastname: Petrovic
authors.forename: N
authors.initials: N
authors.lastname: Breslin
authors.forename: M
authors.initials: M
authors.lastname: Cowan
authors.forename: G
authors.initials: G
authors.lastname: Pelle-Day
authors.forename: E
authors.initials: E
authors.lastname: Cooperstein
authors.forename: L-A
authors.initials: LA
authors.lastname: Baxter-Lowe
mesh_terms: D000293:Adolescent; D017252:CD3 Complex / Q000096:biosynthesis; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods; D007223:Infant; D012008:Recurrence; D012306:Risk; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D017252:CD3 Complex; D007166:Immunosuppressive Agents